Porous base matrix is used for a wide variety of adsorbents, for example, for adsorbents for chromatography or as affinity adsorbents. Of these, affinity adsorbents are able to efficiently purify a target substance or reduce the content of unwanted substances, and are therefore used as medical adsorbents or as adsorbents for purifying antibody drugs. In particular, attention has been focused on adsorbents obtained by immobilizing protein A as an affinity ligand on a porous base matrix as medical adsorbents for the treatment of rheumatism, hemophilia and dilated cardiomyopathy (for example, Non-patent Document 1, Non-patent Document 2).
Meanwhile, attention has been focused on adsorbents obtained by immobilizing protein A as an affinity ligand on a porous base matrix, i.e. adsorbents for purifying antibody drugs, as adsorbents able to specifically adsorb and release immunoglobulin (IgG). Methods for immobilizing a variety of affinity ligands such as protein A on a porous base matrix can be selected from among a variety of immobilization methods, such as cyanogen bromide method, trichlorotriazine method, epoxy method or tresyl chloride method, as indicated in Table 8.1 and FIG. 8.15 of Non-patent Document 3. Of these, it is preferable from an industrial perspective to use the reaction between a formyl group on a porous base matrix and an amino group on an affinity ligand so as to effect immobilization from the perspective of safety and for reasons such as the ease of the immobilization reaction and the fact that it is possible to use proteins or peptides produced by a relatively simple method.
A method in which a polysaccharide gel having vicinal hydroxy groups is oxidized through periodate oxidation so as to generate formyl groups on the sugar chain can be used as a method for introducing formyl groups into a porous base matrix (for example, refer to Non-patent Document 4). The porous base matrix is hereinafter abbreviated to a “sugar chain cleavage-type” porous base matrix. An adsorbent obtained via the method has the advantage of having little ligand leakage. In addition, it is possible to use a method that introduces formyl group via a variety of spacers obtained by, for example, a method that uses glutaraldehyde, such as that disclosed in FIG. 8.15 of Non-patent Document 3, or a method in which periodate is made to act on glyceryl group obtained through the ring opening of epoxy group, such as that disclosed in FIG. 8.15 of Non-patent Document 3 or FIG. 2.13 of Non-patent Document 5. The porous base matrix is hereinafter abbreviated to a “spacer-type” porous base matrix. The adsorbent using the spacer-type porous base matrix having formyl group tends to have relatively high adsorption of the target substance.
In addition, usage in direct hemoperfusion (DHP) methods is anticipated in the field of medical adsorbents for treatment, and it is hoped that base matrix and adsorbents that use base matrix has sufficient strength to withstand use in DHP. Meanwhile, the market for antibody drugs has expanded greatly in recent years; and as a result, upscaling and increased linear speed of antibody drug purification are being actively carried out. With the upscaling and increased linear speed of purification, a need has arisen for the strength of adsorbents, that is, porous base matrix, used in the purification to increase in some cases. If porous base matrix having low strength is used on a large scale and at high linear speeds, compaction of the porous base matrix can occur, which can lead to problems such as liquids being unable to flow. In the past, silica gel-based porous base matrix such as that disclosed in Patent Document 1, agarose-based crosslinked porous base matrix such as that disclosed in Patent Document 2 and cellulose-based porous base matrix such as that disclosed in Patent Document 3 have been known as porous base matrix having high strength.    Patent Document 1: JP6-281638A    Patent Document 2: JP2000-508361T    Patent Document 3: JP1-217041A    Non-patent Document 1: Annals of the New York Academy of Sciences, 2005, vol. 1051, p. 635-646    Non-patent Document 2: American Heart Journal, vol. 152, number 4, 2006    Non-patent Document 3: Affinity Chromatography, written by KASAI Kenichi et al., published by Tokyo Kagaku Dozin Co., Ltd., 1991    Non-patent Document 4: Immunology, 20, 1061, 1971    Non-patent Document 5: Immobilized Affinity Ligand Techniques, Greg T. Hermanson et al., 1992